In 2008 nearly 150,000 cases of
colorectal cancer will be diagnosed in the United
States, while nearly 50,000 people will die
from the disease. The key to overcoming colorectal
cancer is early detection, as treatments for
early stages of disease are readily available
and highly effective. Existing screening methods
tend to suffer from poor specificity or cause
significant patient discomfort. As a result,
many cases of colorectal cancer go undetected
until relatively late stages when the prognosis
is comparatively grim. If a more convenient
and specific means of colorectal cancer detection
were available, many lives could be saved.
Over the past fifteen
years or so, advances in mass spectrometry instrumentation,
computational resources, and experimental techniques
have led to the development of proteomics: the
study of global patterns of protein expression
and modifications under a wide array of biological
conditions. Today, using state-of-the-art mass
spectrometry and proteomics techniques, hundreds
or thousands of proteins can be routinely identified
and quantified from even complex biological
samples such as tissue extracts and serum.
I am now working
with Professor William Dove of Oncology, and
Professor Michael Sussman of the Biochemistry
department, to characterize the Min mouse on
a proteomic level. Individual Min mice have
a loss-of-function mutation in one copy of their
Adenomatous Polyposis Coli gene, which predisposes
them to development of many tumors in their
intestinal tract at an early age. We are using
a variety of quantitative proteomics techniques,
including metabolic labeling with stable isotopes,
to compare protein abundances in tumor versus
normal colonic and intestinal tissues. We are
also surveying serum proteins in an effort to
identify any that are differentially expressed.
This work should improve our understanding of
the molecular basis of tumor development and
should reveal wider physiological effects of
tumor formation. We may also identify proteins
that could serve as possible diagnostic or prognostic
biomarkers for colorectal tumor development.